Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression.

Colorectal cancer (CRC) remains one of the most commonly diagnosed and deadliest types of cancer worldwide. CRC displays a desmoplastic reaction (DR) that has been inversely associated with poor prognosis; less DR is associated with a better prognosis. This reaction generates excessive connective tissue, in which cancer-associated fibroblasts (CAFs) are critical cells that form a part of the tumor microenvironment. CAFs are directly involved in tumorigenesis through different mechanisms. However, their role in immunosuppression in CRC is not well understood, and the precise role of signal transducers and activators of transcription (STATs) in mediating CAF activity in CRC remains unclear. Among the myriad chemical and biological factors that affect CAFs, different cytokines mediate their function by activating STAT signaling pathways. Thus, the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors. Here, we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

High expression of both desmoplastic stroma and epithelial to mesenchymal transition markers associate with shorter survival in pancreatic ductal adenocarcinoma.

Desmoplastic stroma (DS) and the epithelial-to-mesenchymal transition (EMT) play a key role in pancreatic ductal adenocarcinoma (PDAC) progression. To date, however, the combined expression of DS and EMT markers, and their association with variations in survival within each clinical stage and degree of tumor differentiation is unknown. The purpose of this study was to investigate the association between expression of DS and EMT markers and survival variability in patients diagnosed with PDAC. We examined the expression levels of DS markers alpha smooth muscle actin (α-SMA), fibronectin, and vimentin, and the EMT markers epithelial cell adhesion molecule (EPCAM), pan-cytokeratin, and vimentin, by immunohistochemistry using a tissue microarray of a retrospective cohort of 25 patients with PDAC. The results were examined for association with survival by clinical stage and by degree of tumor differentiation. High DS markers expression -α-SMA, fibronectin, and vimentin- was associated with decreased survival at intermediate and advanced clinical stages (p=0.006-0.03), as well as with both poorly and moderately differentiated tumor grades (p=0.01-0.02). Interestingly, the same pattern was observed for EMT markers, i.e., EPCAM, pan-cytokeratin, and vimentin (p=0.00008-0.03). High expression of DS and EMT markers within each clinical stage and degree of tumor differentiation was associated with lower PDAC survival. Evaluation of these markers may have a prognostic impact on survival time variation in patients with PDAC.

Retrospective cohort of pancreatic and Vater ampullary adenocarcinoma from a reference center in Mexico.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) and ampulla of Vater adenocarcinomas (AVAC) are periampullary tumors. These tumors have overlapping symptoms and a common treatment, but present differences in their survival and biology. No recent studies in Mexico have been published that describe the clinicopathological characteristics of these tumors. Therefore, the aim of this study was to describe the clinicopathological characteristics of PDAC and AVAC in patients at a reference center in Mexico. METHODS: A retrospective cohort of patients with PDAC or AVAC was analyzed at our institution (July 2007 to June 2016). Inferential analysis of the clinical data was performed with Student's t-test or a χ2 test with odds ratios (OR) and confidence intervals (CI), depending on the variables. Overall survival was compared using Kaplan-Meier curves with log-rank p values. RESULTS: Forty patients with PDAC and 76 with AVAC were analyzed, including 77 females and 39 males with a mean age of 60.6 years and a mean evolution time of 5.7 months. PDAC patients had more abdominal pain, a larger tumor size and more advanced stages than AVAC patients. In contrast, AVAC patients had more jaundice, a higher percentage of complete resections and higher overall survival. Up to 70% of patients were overweight. PDAC cohort included a higher proportion of smokers. CONCLUSIONS: Our cohort was slightly younger, had a larger percentage of females, and a greater percentage of obese patients than those in many international reports. A high proportion of PDAC patients are diagnosed in advanced stages and have a low likelihood of resectability.